Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

Anti-influenza activity of diazaadamantanes combined with monoterpene moieties Full article

Journal

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Output data

Year: 2017, Volume: 27, Number: 19, Pages: 4531-4535 Pages count : 5 DOI: 10.1016/j.bmcl.2017.08.062

Tags

Diaza-adamantane; Terpene; Influenza; Antivirals; Citronellal; Myrtenal

Authors

Suslov Evgeniy ¹ , Zarubaev Vladimir V. ² , Slita Alexander V. ² , Ponomarev Konstantin ¹ , Korchagina Dina ¹ , Ayine-Tora Daniel M. ³ , Reynisson Johannes ³ , Volcho Konstantin ^1,4 , Salakhutdinov Nariman ^1,4

Affiliations

1	(Данные Web of science) Russian Acad Sci, Novosibirsk Inst Organ Chem, Siberian Branch, Novosibirsk 630090, Russia
2	(Данные Web of science) Pasteur Inst Epidemiol & Microbiol, 14 Mira Str, St Petersburg 197101, Russia
3	(Данные Web of science) Univ Auckland, Sch Chem Sci, Auckland, New Zealand
4	(Данные Web of science) Novosibirsk State Univ, Pirogova 2, Novosibirsk 630090, Russia

The antiviral activity of several diaza-adamantanes containing monoterpenoid moieties against a rimantadine-resistant strain of the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. Hetero-adamantanes containing monoterpene moieties at the aminal position of the heterocycle were found to exhibit lower activity compared to compounds with a diaza-adamantane fragment and a monoterpene moiety linked via an amino group at the 6-position of the hetero-adamantane ring. The highest selectivity index (a ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration) out of 30 was observed for compound 8d, which contains a citronella] monoterpenoid moiety. Diaza-adamantane 8d was superior to its adamantane-containing analog 5 both in its anti-influenza activity and selectivity. Furthermore, 8d has more balanced physicochemical properties than 5, making the former a more promising drug candidate. Modelling these compounds against an influenza virus M2 ion channel predicted plausible binding modes to both the wild-type and the mutant (S31N). (C) 2017 Elsevier Ltd. All rights reserved.

Suslov E. , Zarubaev V.V. , Slita A.V. , Ponomarev K. , Korchagina D. , Ayine-Tora D.M. , Reynisson J. , Volcho K. , Salakhutdinov N.
Anti-influenza activity of diazaadamantanes combined with monoterpene moieties
Bioorganic and Medicinal Chemistry Letters. 2017. V.27. N19. P.4531-4535. DOI: 10.1016/j.bmcl.2017.08.062 WOS Scopus РИНЦ

Published print:

Oct 1, 2017

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